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Glioma is difficult-to-treat because of its infiltrative nature and the presence of the blood-brain barrier. Temozolomide is the only FDA-approved drug for its management. Therefore, finding a novel chemotherapeutic agent for glioma is of utmost importance. Magnolol, a neolignan, has been known for its apoptotic role in glioma. In this work, we have explored a novel anti-glioma mechanism of Magnolol associated with its role in autophagy modulation. We found increased expression levels of Beclin-1, Atg5-Atg12, and LC3-II and lower p62 expression in Magnolol-treated glioma cells. PI3K/AKT/mTOR pathway proteins were also downregulated in Magnolol-treated glioma cells. Next, we treated the glioma cells with Insulin, a stimulator of PI3K/AKT/mTOR signaling, to confirm that Magnolol induced autophagy by inhibiting this pathway. Insulin reversed the effect on Magnolol-mediated autophagy induction. We also established the same in in vivo glioma model where Magnolol showed an anti-glioma effect by inducing autophagy. To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor. Chloroquine efficiently reversed the anti-glioma effects of Magnolol both in vitro and in vivo. Our study revealed the cytotoxic effect of Magnolol-induced autophagy in glioma, which was not previously reported. Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management.
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Antineoplásicos , Glioma , Insulinas , Lignanas , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Lignanas/farmacologia , Lignanas/uso terapêutico , Glioma/tratamento farmacológico , Glioma/metabolismo , Autofagia , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Insulinas/farmacologia , Insulinas/uso terapêutico , Linhagem Celular Tumoral , ApoptoseRESUMO
Mental health wellbeing is a critical element in the overall wellbeing of an individual. Severe mental health issues are directly connected with the individual's functioning and negatively impacts the quality of life. Inpatient psychiatric hospitalization does help significantly in stabilizing the acute serious mental health problems; however, the utility of community partial hospitalization program (PHP) has not been studied extensively. We undertook this study to assess the usefulness of community partial hospitalization program (PHP) in reducing severity of psychosomatic symptoms of patients; to study the epidemiology of the referred patients; and to elucidate the characteristics and predictors of psychosomatic symptom response. 164 patients were assessed by a baseline Behavioral and Symptom Identification Scale-32 (BASIS-32) at a tertiary healthcare center, out of which 82 patients subsequently followed up and were assessed using the same scale and the data was then stratified and compiled. Out of the initial 164 patients, at a 50% adherence rate, 13 patients showed an improvement greater than 30% with a significant co-relation to the race of the patients. Partial Hospitalization Program proved to be moderately effective in improving psychosomatic symptoms, with better results noticed in the White/Caucasian race. We need to consider several variables before generalizing this finding and more studies are needed in this area. However, we are able to highlight this valuable tool in addressing the severe mental health issues in a community-based populations.
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Hospital Dia , Transtornos Mentais , Adulto , Hospitalização , Humanos , Pacientes Internados , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Saúde Mental , Qualidade de VidaRESUMO
BACKGROUND: Severe acute respiratory distress syndrome associated with coronavirus disease-2019 (COVID-19) (CARDS) pneumonitis presents a clinical challenge as regards to the timing of intubation and ambiguity of outcome. There is a lack of clear consensus on when to switch patients from trials of noninvasive therapies to invasive mechanical ventilation. We investigated the effect of the timing of intubation from the time of admission on the clinical outcome of CARDS. AIM AND OBJECTIVE: The aim and objective was to analyze the effect of timing of intubation early (within 48 hours of admission to critical care unit) versus delayed (after 48 hours of admission to critical care unit) on mortality in severe CARDS patients. MATERIALS AND METHODS: A retrospective observational study performed in a 28-bedded COVID-19 intensive care unit of a tertiary care hospital in Pune, India. All patients admitted between April 1, 2020, and October 15, 2020, with confirmed COVID-19 (RT-PCR positive) requiring mechanical ventilation were included in the study. RESULTS: The primary outcome was in-hospital mortality. Among 2,230 patients that were admitted to the hospital, 525 required critical care (23.5%), invasive mechanical ventilation was needed in 162 patients and 147 (28%) of critical care admission were included in the study cohort after exclusion. Seventy-five patients (51%) were intubated within 48 hours of critical care admission (early group) and 72 (48.9%) were intubated after 48 hours of critical care admission (delayed group). With regards to the total of 147 included patients; male patients were 74.1% with a median age of 59 years (interquartile range, 51-68 years). Diabetes (44.9%) and hypertension (43.5%) were the most common comorbidities. Higher admission acute physiology and chronic health evaluation II scores and lower absolute lymphocyte count were observed in patients intubated within 48 hours. The early intubated group had a mortality of 60% whereas the same was observed as 77.7% in delayed intubation group, and this difference was statistically significant (p = 0.02). CONCLUSION: Current study concludes that early intubation is associated with improved survival rates in severe CARDS patients. HOW TO CITE THIS ARTICLE: Zirpe KG, Tiwari AM, Gurav SK, Deshmukh AM, Suryawanshi PB, Wankhede PP, et al. Timing of Invasive Mechanical Ventilation and Mortality among Patients with Severe COVID-19-associated Acute Respiratory Distress Syndrome. Indian J Crit Care Med 2021;25(5):493-498.
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Transmesocolic and transomental hernias (TOHs) are rare types of internal hernia. Both these hernias occurring concurrently in a patient are even rarer. We report a patient with signs of recurrent small-bowel obstruction who was found to have a dual transmesocolic, TOH. Computed tomography imaging and subsequent laparoscopic exploration identified small-bowel loops passing through a defect in the transverse mesocolon behind the stomach to emerge through the gastrohepatic omentum. This was treated successfully by laparoscopy. To the best of our knowledge, this is the first reported case of a combined transmesocolic, TOH undergoing successful laparoscopic repair.
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Traditional management of gallstone pancreatitis (GP) has been to perform cholecystectomy during the same hospital admission after resolution. However, when GP develops in the immediate postoperative period from a major colorectal operation, cholecystectomy may be fraught with difficulty due to the inflammatory response that occurs. Thus, delaying cholecystectomy until the inflammatory response subsides may be worthwhile, and it maximizes the chances of completing the cholecystectomy laparoscopically. We have described our management of 2 patients with GP occurring after colorectal operations, which required proximal diverting ileostomy. In both cases, we deferred management of GP with either endoscopic retrograde cholangiopancreatography (ERCP) or medical conservative measures during the acute attack and performed laparoscopic cholecystectomy during ostomy reversal surgery utilizing the existing ostomy takedown site for port placement. Both patients tolerated this management well.
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Dens in dente is a developmental dental anomaly which poses a challenge for the endodontist due to its complex pulpal anatomy. In this case report, a class 2 dens in dente was managed nonsurgically. A 32-year-old female reported with a palatal swelling and pain in the upper front region of the jaw. On examination, #7 was observed to be malformed and showed a negative pulpal sensibility test. Radiographic and CBCT analysis revealed Ohler's type 2 dens in dente with a periapical radiolucency. In the first visit, invagination was removed using diamond-coated ultrasonic tips, the canal was minimally instrumented, and premixed calcium hydroxide was injected in the canal which accidentally extruded periapically. After two weeks, a draining sinus was observed on the palatal side which when traced, lead to #7. Intracanal dressing was replaced with a mix of powdered calcium hydroxide and saline. The dressing was replaced every two weeks, and radiographs were taken, which revealed the resorption of extruded calcium hydroxide and reduction in the osseous defect. Biodentine was used to obturate the entire canal space. Subsequent follow-up radiographs till 24 months showed significant periapical healing and resorption of extruded calcium hydroxide.
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Context: Bioceramic sealers have improved sealing ability by forming an interfacial apatite layer that chemically bonds the sealer and radicular dentin thus decrease apical leakage. Aim: This study aims to evaluate and compare the apical leakage of Cerafill RCS bioceramic sealer and gutta percha when used with three different obturating techniques. Materials and Methods: Thirty-four extracted single-rooted premolars were decoronated and prepared up to size F3. Then, the specimens were randomly divided into 3 experimental groups (n = 10) cold lateral obturation technique, warm vertical obturation technique, single-cone obturation technique, positive and negative control groups (n = 2), according to the obturation technique used along with a bioceramic sealer. To evaluate apical leakage, all specimens were mounted in a glucose leakage model and assessed at 7 and 14 days using an ultraviolet-visible spectrophotometer. Statistical Analysis: The results were subjected to ANOVA/Kruskal-Wallis ANOVA; followed by post hoc analysis using Bonferroni correction. Results: Significant differences were found in the cumulative leakage of all the three experimental groups. Significantly higher leakage was found in groups obturated using single-cone obturation technique as compared to warm vertical compaction technique at both 7 and 14 days. Conclusions: Warm vertical compaction showed a better sealing result than single-cone obturation techniques at all observation periods.
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BACKGROUND: Implantable cardioverter-defibrillators (ICDs) often have clinically useful battery life remaining when explanted because of upgrades, infection, or patient death. OBJECTIVE: To show that explanted ICDs can be resterilized and reused. DESIGN: Retrospective cohort study. SETTING: Multicenter ICD acquisition and single-center ICD reimplantation. PATIENTS: Indigent persons in India who had class I indications for cardiac resynchronization therapy with an ICD and were unable to afford such a device. MEASUREMENTS: Device longevity after reimplantation, device-related complications, number of appropriate therapies, patient clinical characteristics, and deaths. RESULTS: Eighty-one consecutive consenting patients (mean age, 52.6 years; 66 male patients) received 106 explanted devices. Twenty-two patients received a second device and 3 patients received a third device after the prior one reached replacement voltage. Mean time to ICD replacement was 1287.4 days. Follow-up data were available for 75 of 81 (92.6%) patients. Mean follow-up duration for all devices was 824.9 days. No infectious complications occurred; 1 lead dislodgement and 1 lead fracture required repeated surgery. Appropriate therapy (shocks or antitachycardia pacing) was delivered by 64 of 106 (60.4%) devices in 44 of 81 (54.3%) patients. Nine of 81 (11.1%) patients died; mean time from implantation to death was 771.3 days. LIMITATIONS: This is a retrospective report of a single-center experience with a modest number of patients and devices. Follow-up data were missing for 6 patients. No records were kept of the number of devices obtained through postmortem versus antemortem explantation or whether explantation was due to infection or upgrade. Complete data were not available on exact battery voltage at the time of reimplantation, left ventricular ejection fraction, or number of inappropriate shocks. A control group was not possible. CONCLUSION: Explanted ICDs with 3 or more years of estimated remaining battery life can be reused after they are cleaned and resterilized. These devices functioned normally and delivered life-saving therapies, without an increased risk for complications. These preliminary data deserve further validation and, if confirmed, could have important societal and economic implications. PRIMARY FUNDING SOURCE: None.
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Desfibriladores Implantáveis , Esterilização , Adulto , Idoso , Falha de Equipamento , Reutilização de Equipamento , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Background Complex abdominal wall hernias have proven challenging to manage, and such patients often require abdominal wall reconstruction (AWR). However, in the context of a socialist healthcare service, which is required to provide equal and fair healthcare access to all, the heavy resource burden and non-life-threatening nature of complex abdominal wall hernias mean that this patient group may not be prioritised. In this paper, we outline the significant quality of life (QoL) burden on patients requiring AWR and the importance of quality improvement projects (QIPs) in establishing and streamlining their care as a robust, transferable model across centres. Methodology We undertook the creation of a regional AWR multidisciplinary team meeting and referral proforma, establishing a joint clinic between the Plastics and General Surgery teams and registering a standard operating procedure for the use of progressive pneumoperitoneum in a subset of AWR patients. We collected qualitative data using questionnaires sent out to clinicians and patients as well as used recognised outcome scales (pre- and post-operative European Hernia Society Quality of Life score, otherwise known as EuraHS-QoL score, and post-operative Carolinas Comfort Scale score) to assess responses to QIPs. Results Both clinicians and patients reported positive feelings towards the implemented changes, and scores following progressive pneumoperitoneum showed significant improvement. Conclusions Therefore, we propose that QIPs have a significant role in the establishment and streamlining of services for patients requiring AWR. Through the repeated use of QIPs, a robust, transferable model could be produced, which could then be shared with other regional specialist centres nationwide. As such, effective care could be offered equally to AWR patients for improved outcomes and reduced strain on healthcare resources.
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Spinal Cord Stimulation (SCS) with leads embedded in the epidural space has become a recognized and effective clinical therapy for chronic pain relief. Leads with multiple electrodes placed close to the spinal cord allow targeted stimulation. This paper presents a novel current steering method to achieve targeted spinal cord stimulation by determining the optimal current sourced through a set of electrodes to maximize current density in a specified region of the spinal cord. The method provides a flexibility for personalized pain relief therapy, while minimizing stimulation in unwanted regions. The paper proposes a new optimization problem to achieve current steering. The optimization problem uses a solution of the Poisson equation evaluated using Finite Element Analysis (FEA) over a geometric model of the spinal cord and the embedded leads. The solution to the optimization problem determines the optimal current sourced through a set of electrodes to achieve a targeted stimulation.
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Introduction: The peripheral nervous system has a complex anatomical structure. Stimulation of nerve fibers in the peripheral nervous system depends on the fiber diameter and myelination as well as its location within the nerve, packing fraction and fascicle distribution within the nerve bundle. This paper analyzes the impact of the variation in peripheral nervous system anatomy and the distance of the stimulating electrodes on the probability of generating an action potential. Methods: A mathematical model for effective fascicle conductivity has been developed to capture the variation in the packing fraction and fiber diameter. A linear activating function is utilized to analyze the impact of this effective conductivity and fascicle distribution as an indicator of generating an action potential. Results: Finite element simulations are performed for the nerve-electrode configuration to evaluate the electric field. The simulation results are used to analyze the activating function for different packing fractions and type of nerve fibers. The effect of electrode distance on activating function and the total current through a nerve bundle has also been studied. Discussion: The simulation results indicate that the peripheral nerve anatomy and electrode distance have a significant effect on the action potential generation.
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BACKGROUND: Sealer penetration into dentinal tubules eliminates the pathways for bacterial leakage and entombs intratubular bacteria. AIM: The aim of this study was to evaluate and compare the depth of radicular dentinal tubule penetration of five root canal sealers using confocal laser scanning microscopy. METHODS: Fifty freshly extracted single-rooted maxillary anterior teeth were used. After decoronation at the cementoenamel junction, they were prepared to ProTaper size F3. After irrigation with 5 mL smear clear, 5 mL 5% sodium hypochlorite and 5 mL distilled water alternatively, the samples were randomly divided into five groups (n = 10) and obturated by lateral compaction technique using the test sealers labeled by fluorescent rhodamine B dye (Mayor Diagnostics, Mumbai, India). Zinc oxide eugenol (ZOE) (Prime Dental Products), EndoREZ (Ultradent), Sealapex (SybronEndo), AH Plus (Dentsply Maillefer), and MTA-Fillapex (Angelus) formed the test groups. Teeth were then positioned in blocks of orthodontic resin. Three horizontal sections of 1-mm representing coronal middle and apical thirds were made and examined with Zeiss (laser scanning microscope [LSM] 780) confocal LSM. Images were analyzed using ZEN 2.1 software. STATISTICAL ANALYSIS: Data were recorded and subjected to statistical analysis using one-way ANOVA test. RESULTS: Maximum penetration depth was demonstrated by AH Plus in the coronal and apical thirds, MTA-Fillapex in the middle thirds, while minimum penetration depth was seen in ZOE in the coronal and middle thirds and Sealapex in the apical thirds. None of the root canal sealers were able to penetrate the complete depth of radicular dentinal tubules. CONCLUSION: While AH Plus and MTA-Fillapex showed the highest penetration into radicular dentinal tubules, ZOE and Sealapex demonstrated the least penetration.
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Biochemical evaluation of cell-matrix interaction using conventional labelling techniques often possesses limitations due to dye entrapment. In contrast, Raman spectroscopy guided approach offers label-free determination of cell-matrix biochemistry. Herein, gelatin (Gel) matrices modified with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/ N-Hydroxysuccinimide (EDC/NHS) and glutaraldehyde (GTA) was used as standards for comparative evaluation. Raman spectroscopy was deployed as a label-free approach to investigate interaction of cells with Gel hydrogels. Raman-based approach assisted in evaluation of cell-matrix interactions by identifying key biomolecular signatures retrospecting the fact that L929 fibroblast cells portrayed excellent growth and proliferation kinetics in crosslinked Gel as compared to its bare counterpart. EDC crosslinked hydrogels exhibited superior cell proliferation than its GTA counterparts. Cell proliferation on differentially crosslinked gel was also confirmed using standard MTT Assay and Rhodamine-DAPI staining thus corroborating the fact that Raman spectroscopy can be deployed as a superior label-free alternative towards real-time determination of cell proliferation and growth.
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Fibroblastos/química , Gelatina , Hidrogéis , Animais , Linhagem Celular , Reagentes de Ligações Cruzadas , Camundongos , Análise Espectral RamanRESUMO
Context: This study was carried out to assess the currently available composite systems in India for resistance to fracture in teeth with large cavities. Aim: To evaluate the fracture toughness of weakened maxillary premolars restored by contemporary composites. Settings and Design: In-vitro study was done in the department of conservative dentistry and endodontics. Materials and Methods: Freshly extracted 44 human maxillary bicuspids were randomly divided into four groups where Group I included intact teeth. The teeth in the other three groups were subjected to a standardized mesio-occluso-distal cavity preparation. The cavities were filled in Group II with bioactive, nanohybrid composite with Giomer chemistry (Beautifil II LS, Shofu Inc., Kyoto, Japan), in Group III with highly filled, nanohybrid composite (Prevest Fusion Universal, Prevest DenPro Limited, Jammu, India) and in Group IV with fiber-reinforced composite with optimized fiber-aspect ratio technology (everX Posterior, GC EUROPE N. V., Leuven, Belgium). All the specimens were then subjected to thermocycling followed by incubation procedures. Fracture resistance was measured in Newton (N) using the universal testing machine. Statistical Analysis Used: Data obtained were tabulated and subjected to one-way analysis of variance (ANOVA) test followed by Tukey's test. Results: Highest mean fracture resistance was observed with Group I (2294.06), followed by Group II (1708.72), Group IV (1195.82), and Group III (825.38). One-way ANOVA test showed a statistically significant difference (P ≤ 0.05) between all the four groups. Post hoc Tukey test was used for intergroup comparison and showed significant difference (P ≤ 0.05) in mean fracture resistance between groups. Conclusion: The results suggest that the highest compressive fracture resistance was shown by Group II (Beautifil II LS composite resin).
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The overlap between inflammatory bowel disease (IBD) and psychiatric disorders has been studied extensively. We reviewed the limited literature targeting the complex relationship between IBD and psychiatric disorders in children and adolescents. Findings from this review were compared with findings from available studies in adults. Results reflecting an association between IBD and psychiatric illnesses were observed in children and adolescents and were consistent with results in adults. In adults with IBD, many studies have reflected the advantages of psychotherapeutic treatment, including faster recovery, improved quality of life, and reduced health care use. Unfortunately, such studies are scarce in the child and adolescent population. Psychopharmacologic studies also are limited in adult and pediatric populations. At this time, the literature on treatment of the pediatric IBD population remains minimal, and the need to study screening and treatment modalities is critical.
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Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/psicologia , Transtornos Mentais/epidemiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/terapia , Prevalência , Psicoterapia , Estados Unidos/epidemiologiaRESUMO
The answer for treating pathologic aggression (PA) in children on inpatient psychiatry units (based on various factors like severity of aggression and co-morbidities) is less likely to be restrictive interventions or sedating the patient. Using seclusion and restraints or medications to calm down the aggression is not free of adverse consequences. A protocol is needed to safely and effectively address aggressive and violent children and adolescents seen very commonly in psychiatry inpatient units.
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Terapia Comportamental/métodos , Terapia Combinada/métodos , Transtorno da Conduta/tratamento farmacológico , Transtorno da Conduta/terapia , Comportamento Cooperativo , Resolução de Problemas , Adolescente , Serviços de Saúde do Adolescente , Criança , Serviços de Saúde da Criança , Pré-Escolar , Protocolos Clínicos , Humanos , Serviços de Saúde Mental , Modelos Psicológicos , Restrição Física/métodos , Isolamento SocialRESUMO
CONTEXT: Studying in detail the root canal morphology specific to the Indian mandibular molars will help discern whether the root canal anatomy patterns resemble those reported internationally or are different from it. AIM: The aim is to study the root canal anatomy of Indian permanent mandibular first, second, and third molar teeth using a tooth clearing technique. METHODS: The root canals of a total of 300 extracted Indian mandibular molars consisting of 100 first, second, and third molars each were accessed and injected with India ink, after which they were subjected to the clearing technique. STATISTICAL ANALYSIS: Data was analyzed using descriptive statistics for the computation of percentages using SPSS version 21. RESULTS: Of the hundred first molars, 90% of teeth were two rooted with three canals, 79% had two apical foramina. 70% mesial roots of the three-rooted type showed Type I, whereas 100% distal roots and distolingual roots showed Type I Vertucci's anatomy. About 70% mesial roots of two roots showed Type II and 90% distal canals showed Type I configuration. Among the second molars, five (5%) were single-rooted, ninety-one (91%) teeth were two rooted and four (4%) had three roots. Among the mandibular third molars, fifteen (15%) teeth had one root, sixty-three (63%) teeth had two roots, eighteen (18%) teeth had three roots, and four (4%) teeth had four roots. CONCLUSIONS: The root canal anatomic features of mandibular molars showed differences in the frequency of particular anatomic types as compared to mandibular molars from other racial backgrounds. Further comparative studies on inter-racial anatomic characteristics from various geographic locations would be beneficial.
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INTRODUCTION: Endodontic failure resolves after complete removal of obturating material followed by disinfection, cleaning, shaping and three-dimensional obturation. MATERIALS AND METHODS: Seventy single-rooted mandibular premolars, with single oval-shaped root canal were included. They were decoronated at a length of 16 mm from the apex. Shaping and cleaning were performed, and obturation was done using the warm lateral compaction technique. The teeth were divided into seven groups according to retreatment procedures (Hand files; ProTaper Universal retreatment files; MTwo® Retreatment system; R-Endo® Retreatment system; ProTaper Universal retreatment files with solvent and ultrasonics; MTwo® R with solvent, and ultrasonics and R-Endo® with solvent and ultrasonics). The data were obtained and subjected to the statistical analysis. RESULTS: All instrumentation techniques left obturating material with least in Group 6 and maximum Group 5. The mean time taken for complete retreatment procedure was minimum in Group 2 and maximum with Group 1. CONCLUSION: MTwo® R with solvent and ultrasonics, R-Endo®, and R-Endo® with solvent and ultrasonics were effective in gutta-percha removal from coronal third, middle third, and apical third, respectively. Significance: Nonsurgical endodontic retreatment using rotary files helps in gaining access to infected teeth. During retreatment procedure, this helps disinfectant to reach in critical areas of the root canal system, thereby decreasing the microbial load, leading to achieve healthy periradicular tissues.
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AIM: The aim of this preliminary study was to compare outcomes of two regenerative endodontic protocols in necrotic teeth with open apices. METHODOLOGY: Forty teeth with open apices in patients with an age range of 15-54 were randomly distributed in two groups: group 1, with whole blood clot in the canal (n=20) and group 2, whole blood with Platelet rich plasma (PRP) in the canal (n=20). Clinical and radiological follow up assessments were undertaken over a period ranging from 6 months to one year. Radiographic Root Area (RRA) was measured using the freeware ImageJ. Statistical analysis was performed using the independent samples t test and the Chi-squared test, the significance level was set at p=0.05. RESULTS: There was no difference in the percentage change in RRA between the PRP group and whole blood-clot + PRP group. CONCLUSION: Whole blood clot and PRP are comparable on the grounds of percentage change in RRA and there is no statistically significant difference between the two in a follow-up period of up to one year.